"To our surprise, it happened to be one of the Polycomb-group proteins," said Zhang. "We've uncovered a new mechanism used by these well-characterized proteins."

The new findings have implications for epigenetics, which is the study of transcriptional control that does not involve DNA sequence and that can be inherited from one generation of cells to another. Along with ubiquitination, epigenetic modifications also include histone methylation, acetylation and DNA methylation.

"The PcG silencing system is one of the best-studied model of epigenetic regulation systems," said Zhang.

PcG proteins function in protein complexes to repress transcription of genes that are likely to include key regulators of the cell cycle.

The new study demonstrated that a gene normally silenced by the complex becomes switched on in cells when one of the PcG proteins essential for the ubiquitination of H2A has been eliminated, Zhang said.

"Although the mechanism by which H2A ubiquitination contributes to PcG silencing is still unknown, the identification of the responsible enzyme should allow us to better understand the PcG silencing system and how it relates to human disease, such as cancer," said Zhang.

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Contact: L.H. Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
29-Sep-2004